The health of the oral cavity is maintained by salivary secretions. The principal function of salivary glands is to produce these complex fluids. We have utilized a variety of tools to understand saliva formation and the pathologic processes that alter normal secretory events. During this reporting period, much of our effort has been directed at using recombinant adenoviruses to transfer aquaporin (AQP; water channel) genes to epithelial cells in order to increase their water permeability. Eventually, we hypothesize that this strategy could be used to correct the irreversible damage suffered by patients whose salivary glands are exposed to ionizing radiation during treatment for head and neck cancer. Radiation is a key component of therapy for such cancers, however, it destroys the fluid secreting acinar cells while the relatively water-impermeable, salt- absorbing ductal cells survive. Our second major area of study this year was related to the systemic secretion of products of genes transferred to the salivary glands. We hypothesized early that because salivary glands are naturally secretory, and are capable of producing large amounts of protein for export, we could utilize the glands to manufacture the products of transferred genes for eventual therapeutic use elsewhere in the body, ie. besides through saliva into the upper gastrointestinal tract.